title: Piperine, a Bioactive Component of Pepper Spice Exerts Therapeutic Effects on Androgen Dependent and Androgen Independent Prostate Cancer Cells.
abstract: Prostate cancer is the most common solid malignancy in men, with 32,000 deaths annually. Piperine, a major alkaloid constituent of black pepper, has previously been reported to have anti-cancer activity in variety of cancer cell lines. The effect of piperine against prostate cancer is not currently known. Therefore, in this study, we investigated the anti-tumor mechanisms of piperine on androgen dependent and androgen independent prostate cancer cells. Here, we show that piperine inhibited the proliferation of LNCaP, PC-3, 22RV1 and DU-145 prostate cancer cells in a dose dependent manner. Furthermore, Annexin-V staining demonstrated that piperine treatment induced apoptosis in hormone dependent prostate cancer cells (LNCaP). Using global caspase activation assay, we show that piperine-induced apoptosis resulted in caspase activation in LNCaP and PC-3 cells. Further studies revealed that piperine treatment resulted in the activation of caspase-3 and cleavage of PARP-1 proteins in LNCaP, PC-3 and DU-145 prostate cancer cells. Piperine treatment also disrupted androgen receptor (AR) expression in LNCaP prostate cancer cells. Our evaluations further show that there is a significant reduction of Prostate Specific Antigen (PSA) levels following piperine treatment in LNCaP cells. NF-kB and STAT-3 transcription factors have previously been shown to play a role in angiogenesis and invasion of prostate cancer cells. Interestingly, treatment of LNCaP, PC-3 and DU-145 prostate cancer cells with piperine resulted in reduced expression of phosphorylated STAT-3 and Nuclear factor-κB (NF-kB) transcription factors. These results correlated with the results of Boyden chamber assay, wherein piperine treatment reduced the cell migration of LNCaP and PC-3 cells. Finally, we show that piperine treatment significantly reduced the androgen dependent and androgen independent tumor growth in nude mice model xenotransplanted with prostate cancer cells. Taken together, these results support further investigation of piperine as a potential therapeutic agent in the treatment of prostate cancer.
authors.affiliation: Department of Biomedical Sciences, University of Illinois, College of Medicine, Rockford, Illinois, United States of America.
authors.forename: Abhilash
authors.initials: A
authors.lastname: Samykutty
authors.forename: Aditya Vittal
authors.initials: AV
authors.lastname: Shetty
authors.forename: Gajalakshmi
authors.initials: G
authors.lastname: Dakshinamoorthy
authors.forename: Mary Margaret
authors.initials: MM
authors.lastname: Bartik
authors.forename: Gary Leon
authors.initials: GL
authors.lastname: Johnson
authors.forename: Brian
authors.initials: B
authors.lastname: Webb
authors.forename: Guoxing
authors.initials: G
authors.lastname: Zheng
authors.forename: Aoshuang
authors.initials: A
authors.lastname: Chen
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Kalyanasundaram
authors.forename: Gnanasekar
authors.initials: G
authors.lastname: Munirathinam
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D052117:Benzodioxoles / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010880:Piperidines / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D000470:Alkaloids; D000728:Androgens; D052117:Benzodioxoles; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D017430:Prostate-Specific Antigen; C008922:piperine